Gene

RET

ret proto-oncogene

Explore in graph →CI-GENE-00023348HGNC:9967 ENSG00000165731 NCBI 5979 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (99)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–50 of 99 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
RET Fusion3
Agerafenib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	3	accepted

Cohorts

Alteration frequency by cohort (117)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved117 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Colorectal Cancer (MSK, Cancer Discovery 2022) coadread_mskresistance_2022	Colorectal Adenocarcinoma	Ssm

Literature

Linked publications (30)

25 per page, newest first.

pubmedPublishedShowing 1–25 of 30 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer.
· N Engl J Med · 2023 · PMID 37870969 · validated civic_curation pubmed
Efficacy of Selpercatinib in RET-Altered Thyroid Cancers.
· N Engl J Med · 2020 · PMID 32846061 · validated civic_curation pubmed
Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study.
· Lancet Oncol · 2021 · PMID 34118197 · validated civic_curation pubmed
Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study.
· Lancet Diabetes Endocrinol · 2021 · PMID 34118198 · validated civic_curation

RET Fusion6
Everolimus + VandetanibCombination	Lung Adenocarcinoma	Predictive	C	Supports Sensitivity Response	2	accepted	EID1622 Case report of a 74-year old woman with EGFR- and ALK-negative lung adenocarcinoma. FISH identified a deletion of 5'RET (FISH, indicating RET-gene rearrangement) and genomic testing confirmed a fusion… (full text at CIViC) PMID 25982012 · Subbiah et al., 2015 · Open in CIViC	civic
Pralsetinib	Solid NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	2	submitted	EID11265 In the phase 1/2 clinical trial NCT03037385, one arm assessed the therapeutic benefit of the selective RET inhibitor pralsetinib across a range RET fusion positive solid tumors, excluding NSCLC and th… (full text at CIViC) PMID 35962206 · Subbiah et al., 2022 · Open in CIViC	civic
Selpercatinib	Malignant Lung Neoplasm	Predictive	B	Supports Sensitivity Response	3	submitted	EID7067 In this phase 1 trial, 57 patients with RET fusion- or mutation positive cancers were treated in 7 dose levels. Among patients with RET-Fusion positive NSCLC, objective response rates were 65% (n = 17… (full text at CIViC) Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	3	submitted	EID6948 A patient with a KIF5B::RET fusion positive NSCLC with brain metastases who had acquired resistance to alectinib experienced a dramatic response to the selective RET inhibitor selpercatinib (LOXO-292)… (full text at CIViC) PMID 29912274 · Subbiah et al., 2018 · Open in CIViC	civic
〃	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	2	submitted	EID12814 Preclinical data demonstrated Ba/F3 cells transformed with KIF5B::RET were IL3 growth independent, and sensitive to selpercatinib with an IC50 of 17.5 +/- 0.7 nM, which the authors considered sensitiv… (full text at CIViC) PMID 37376747 · Szymczak et al., 2023 · Open in CIViC	civic
Vandetanib	Lung Adenocarcinoma	Predictive	C	Supports Sensitivity Response	2	accepted	EID698 A case study of a patient with EGFR, KRAS, BRAF, HER2, ALK, ROS1 and MET negative adenocarcinoma of the lung. FISH analysis revealed a KIF5B-RET fusion. The RET inhibitor Vandetanib led to remission i… (full text at CIViC) PMID 23584301 · Gautschi et al., 2013 · Open in CIViC	civic

RET Fusion6

Everolimus + VandetanibCombination

Lung Adenocarcinoma

Predictive

Supports Sensitivity Response

accepted

EID1622

Case report of a 74-year old woman with EGFR- and ALK-negative lung adenocarcinoma. FISH identified a deletion of 5'RET (FISH, indicating RET-gene rearrangement) and genomic testing confirmed a fusion… (full text at CIViC)

PMID 25982012 · Subbiah et al., 2015 · Open in CIViC

RET Fusion + RET G810A2
Lenvatinib + PonatinibSubstitutes	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID4853 We established inducible KIF5B-RET transgenic mice and KIF5B-RET-dependent cell lines for preclinical modeling of KIF5B-RET-associated lung adenocarcinoma. By culturing cells with increasing concentra… (full text at CIViC) PMID 27496134 · Huang et al., 2016 · Open in CIViC	civic
Vandetanib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Does Not Support Resistance	3	submitted	EID4852 We established inducible KIF5B-RET transgenic mice and KIF5B-RET-dependent cell lines for preclinical modeling of KIF5B-RET-associated lung adenocarcinoma. By culturing cells with increasing concentra… (full text at CIViC) PMID 27496134 · Huang et al., 2016 · Open in CIViC	civic

RET Fusion + RET V804L2
Cabozantinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Does Not Support Resistance	3	submitted	EID4851 We established inducible KIF5B-RET transgenic mice and KIF5B-RET-dependent cell lines for preclinical modeling of KIF5B-RET-associated lung adenocarcinoma. By culturing cells with increasing concentra… (full text at CIViC) PMID 27496134 · Huang et al., 2016 · Open in CIViC	civic
Dasatinib	Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS	Predictive	D	Supports Resistance	2	submitted	EID7515 In an in vitro kinase study, the recombinant RET V804L mutant kinase demonstrated resistance to dasatinib treatment at concentrations of 1μM and 10μM (activity %: 101 and 91) when compared to wild typ… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC	civic

RET C609Y2
(predisposing)	Thyroid Gland Medullary CarcinomaALIAS	Predisposing	B	Supports Predisposition	4	accepted	EID2913 Study of a family with three generations of history indicating co-segregation of RET C609Y and multiple endocrine neoplasia type 2A, many of whom exhibited medullary thyroid cancers specifically. 22 … (full text at CIViC) PMID 19472011 · Calva et al., 2009 · Open in CIViC	civic
〃	Thyroid Gland Medullary CarcinomaALIAS	Predisposing	E	Supports Uncertain Significance	3	submitted	EID2914 This study performed various functional characterizations of several RET mutations known to occur as pathogenic germline variants in multiple endocrine neoplasia type 2 and medullary thyroid cancer. S… (full text at CIViC) PMID 16715139 · Mise et al., 2006 · Open in CIViC	civic

RET C634R2
(diagnostic)	Thyroid Gland Medullary CarcinomaALIAS	Diagnostic	B	Supports Positive	3	submitted	EID4894 Sixty-nine individuals from 12 different families presented a codon 634 mutation, the most prevailing missense mutation in our series. The specific mutations identified were C634Y (n = 49), C634R (n =… (full text at CIViC) PMID 12788868 · Puñales et al., 2003 · Open in CIViC	civic
(oncogenic)	Malignant NeoplasmALIAS	Oncogenic	D	Supports Oncogenicity	3	accepted	EID11874 In a colony formation assay with NIH3T3 cells, RET C634R was used as a positive control (called MEN2A after its association with that disease). Cells transformed with C634R showed significant colony f… (full text at CIViC) PMID 9191060 · Ceccherini et al., 1997 · Open in CIViC	civic

RET C634W3
Axitinib	Thyroid Gland Medullary CarcinomaALIAS	Predictive	D	Supports Resistance	—	submitted	EID3694 In an in vitro study, a MTC-TT cell line expressing RET C634W mutation (endogenous) demonstrated resistance to axitinib treatment (IC50: 1.56uM). Resistance was determined by assessing cell viability… (full text at CIViC) PMID 21470995 · Verbeek et al., 2011 · Open in CIViC	civic
Motesanib	Thyroid Gland Medullary CarcinomaALIAS	Predictive	D	Supports Resistance	3	accepted	EID75 Medullary thyroid cancer cells with RET C634W mutation are insensitive to motesanib, compared to wild-type RET. PMID 21422803 · Coxon et al., 2012 · Open in CIViC	civic
Regorafenib Anhydrous	Gastrointestinal Stromal Tumor	Predictive	D	Supports Sensitivity Response	—	submitted	EID3695 In an in vitro study, a TT cell line expressing RET C634W mutation demonstrated increased sensitivity to regorafenib treatment (IC50: 34nM vs. 560-3269nM) compared to HepG2, SW620, Colo-205 or A375 ce… (full text at CIViC) PMID 21170960 · Wilhelm et al., 2011 · Open in CIViC	civic